Four New Research Studies Describe Experimental Immunotherapies for Alzheimer's

- Two Target Tau; Two May Reduce Tau Though Their Target Was
Amyloid -

HONOLULU, July 13 /PRNewswire-USNewswire/ -- The primary
therapeutic target in Alzheimer's disease has been the beta amyloid
peptide, which clusters outside cells in the brain to form sticky
clumps known as plaques. Recently, more attention has been given to
the tau protein, which aggregates inside the brain cells of people
with Alzheimer's, forming neurofibrillary tangles. Precisely how
these proteins interact in causing the disease is unclear.

Four new research studies reported today at the Alzheimer's
Association International Conference on Alzheimer's Disease 2010
(AAICAD 2010) in Honolulu, HI describe experimental immunotherapies
for Alzheimer's two of which target tau directly and two of which
may reduce tau even though their primary target was beta
amyloid.

"It is very important that we have a variety of therapeutic
targets in the fight against Alzheimer's disease," said William
Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's
Association. "The more opportunities that we investigate to
intervene and change the relentless and progressive course of
Alzheimer's, the better chance that we will find something that
works."

"Importantly, these studies teach us more not only about
tau-targeted therapies but also about the progression of
Alzheimer's disease," Thies added. "It may be that amyloid changes
in the brain happen early in the disease and tau-related changes
happen 'downstream' where they have a more direct effect on
cognitive function. However, this is still to be determined."

"We need more basic research about what causes Alzheimer's, as
well as therapy-related studies, to fill the front end of the drug
pipeline and get us the better treatments and prevention strategies
that we so desperately need to head off the epidemic of
Alzheimer's," Thies said.

Beta Amyloid Immunotherapy with Bapineuzumab in Alzheimer's May
Also Reduce Tau

Bapineuzumab (Janssen Alzheimer Immunotherapy and Pfizer) is an
antibody to the beta amyloid plaques that are associated with
Alzheimer's disease, and is currently in Phase 3 testing as a
treatment for mild to moderate Alzheimer's. An abnormal form of the
tau protein known as phospho-tau (P-tau) forms into tangles which
are the other established lesions in the brain of people with
Alzheimer's. The amount of P-tau in cerebrospinal fluid (CSF) is
believed to be a marker of active loss of brain cells in people
with Alzheimer's; prior studies have shown increases in P-tau in
people with mild cognitive impairment who later develop
Alzheimer's. P-tau was studied as a therapeutic biomarker in the
Phase 2 clinical trials of bapineuzumab.

The pooled exploratory analysis reported at AAICAD 2010 by Kaj
Blennow, MD, PhD, of the University of Gothenburg, Sweden, and
colleagues included a subgroup of participants from two randomized,
multicenter, double-blind, placebo-controlled,
multiple-ascending-dose studies conducted in the United States
(Study 201) or in the United Kingdom and Finland (Study 202). Study
201 enrolled 35 patients (20 bapineuzumab, 15 placebo) in the CSF
substudy, and Study 202 enrolled 11 patients (7 bapineuzumab, 4
placebo) in the CSF substudy. CSF was collected at baseline and 2
weeks after the week 52 infusion.

The researchers found that Study 201 showed a trend (p=0.0564)
towards a decrease in CSF P-tau in bapineuzumab-treated compared
with placebo-treated cases. In Study 202, no significant treatment
effects were seen. When they combined data from both studies, they
found a statistically significant decrease (p=0.0270) in P-tau in
bapineuzumab-treated compared with placebo-treated patients.

"These observations suggest that immunotherapy treatment
targeting amyloid may also alter neurodegenerative processes that
occur later in the disease process and that are more directly
associated with loss of function," Blennow said. "However, this was
a small study and these findings need to be confirmed."

Another Immunization Therapy for Alzheimer's with Beta Amyloid
Also Reduces Tau

AN1792 (Elan) showed early promise as a beta amyloid
immunotherapy for Alzheimer's. In 2002, a Phase 2 trial reported
that about 6 percent of participants developed serious brain
inflammation symptoms resembling meningoencephalitis. The trial was
stopped as was further clinical development. However, participants
in the first AN1792 trial continue to be observed.

Delphine Boche, PhD, of the University of Southampton's School
of Medicine, UK, and colleagues studied the levels of beta amyloid
and phospho-tau in six regions of cerebral grey matter that are
affected by Alzheimer's pathology in the brains of 10 people with
Alzheimer's who were immunized with AN1792 and compared the
findings with 28 unimmunized Alzheimer cases. They had previously
shown a reduction of beta amyloid in people treated with AN1792 and
now looked to see if it had any effect on tau.

The researchers found statistically significant reductions in
tau and beta amyloid in the immunized patients compared with
untreated Alzheimer's. The reduction in tau appeared to be
specifically in the dendrites, which are the branched projections
of a neuron that conduct the electrochemical stimulation received
from other nerve cells to the cell body. In contrast, tau in the
bodies of the nerve cells, where the tangles form, seemed
unaffected.

"The findings show that treatment aimed at beta amyloid may also
modify tau changes in Alzheimer's," Boche said. "The lack of change
in tau in the bodies of nerve cells might explain why the people in
the original AN1792 trial didn't experience an improvement in
cognitive functioning even though we saw amyloid clearance."

"This study demonstrates a link between these two
Alzheimer's-related proteins, which has been suspected but not
clearly demonstrated in the human brain. The findings give us more
basic information about the interaction between beta amyloid and
tau in Alzheimer's and may clarify how the disease progresses in
the brain," Boche said.

Tau Antibodies Reduce Brain Tangles in Alzheimer-Model
Mice

Allal Boutajangout, PhD, of the New York University School of
Medicine, and colleagues previously reported that active tau
immunization clears tau tangles from the brain and reduces or
prevents functional impairments in two different tangle-model mice.
In a study reported at AAICAD 2010, they assessed the efficacy of
passive immunization for 13 weeks with the PHF1 antibody to tau in
a mouse model of Alzheimer's tangles.

The researchers found that weekly injections of PHF1 in the
tangle mice reduced the amount of tau aggregates in the brain and
decreased functional impairment. The treated mice performed better
than controls on the traverse beam task (p<0.03), and had 58
percent less tau pathology in the hippocampus (p=0.02). Plasma
levels of PHF1 were inversely related to levels of tau pathology in
two brain sections - the brain stem (p<0.01) and motor cortex
(p=0.06) - indicating that higher dose of antibodies may have a
greater therapeutic effect.

"Targeting hyperphosphorylated tau by immunotherapy is emerging
as a promising approach to treat tau-related diseases such as
Alzheimer's disease and frontotemporal dementia," Boutajangout
said. "Further studies are needed to determine the feasibility of
this approach with other tau antibodies and in different tangle
models that more closely resemble Alzheimer's."

Alzheimer's Tau Vaccine Shows Promise in a New Rat Model of the
Disease

Scientists led by Prof. Michal Novak, MDV, PhD, DSc, of the
Institute of Neuroimmunology, Slovak Academy of Sciences,
Bratislava, Slovakia and Co-Founder and Chief Scientific Officer of
the Axon Neuroscience GmbH, Vienna, Austria, have developed a new
transgenic rat model of Alzheimer's that, according to Novak, for
the first time expresses non-mutated tau and generates Alzheimer's
neurofibrillary tangles. Axon is using the rat for early,
preclinical development of an Alzheimer's tau vaccine.

In a study reported at AAICAD 2010, Axon transgenic rats were
immunized with phospho-tau. The scientists measured changes in
functions related to behavior and learning, levels of
phosphorylated tau in cerebrospinal fluid, and level of tangle
pathology in the rat brains. They found that tau immunization
significantly reduced the amount of insoluble tau, prevented
development of neurofibrillary tangles, and produced a
statistically significant delay of progressive impairment in
learning behaviors.

"The Axon Alzheimer Rat may offer new avenues in developing the
next generation of therapies and diagnostics for Alzheimer's,"
Novak said.

About AAICAD

The Alzheimer's Association International Conference on
Alzheimer's Disease (AAICAD) is the world's largest conference of
its kind, bringing together researchers from around the world to
report and discuss groundbreaking research and information on the
cause, diagnosis, treatment and prevention of Alzheimer's disease
and related disorders. As a part of the Alzheimer's Association's
research program, AAICAD serves as a catalyst for generating new
knowledge about dementia and fostering a vital, collegial research
community.

About the Alzheimer's Association

The Alzheimer's Association is the leading voluntary health
organization in Alzheimer care, support and research. Our mission
is to eliminate Alzheimer's disease through the advancement of
research, to provide and enhance care and support for all affected,
and to reduce the risk of dementia through the promotion of brain
health. Our vision is a world without Alzheimer's. Visit
www.alz.org or call 800-272-3900.

Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment.